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作 者:李雅慧[1] 黎怀星[2] 董诗源[1] 余超[1] 姜雨[1] 孙树汉[3]
机构地区:[1]国家食品药品监督管理局保健食品审评中心,北京100061 [2]中科院上海生命科学研究院营养科学研究所,上海200031 [3]第二军医大学基础医学部医学遗传学教研室,上海200433
出 处:《第二军医大学学报》2006年第10期1067-1071,共5页Academic Journal of Second Military Medical University
基 金:国家自然科学基金(30370802).~~
摘 要:目的:观察Resistin蛋白对3T3-L1脂肪细胞葡萄糖摄取的影响并探讨其引发胰岛素抗性的可能机制。方法:(1)采用放射免疫测定法检测低、正常及高表达Retn基因的3T3-L1脂肪细胞在基础状态及胰岛素刺激下的葡萄糖摄取水平。(2)采用RT-PCR和实时荧光定量RT-PCR法测定低、正常和高表达Retn基因的3T3-L1脂肪细胞中几种葡萄糖转运信号蛋白,包括胰岛素受体底物1(IRS-1)、磷脂酰肌醇3激酶(PI-3K)、丝/苏氨酸激酶2(AKT-2)、葡萄糖转运子4(GLUT-4)、丝裂原活化蛋白激酶p38(p38MAPK)及糖原合成酶激酶3β(GSK-3β)的表达。结果:(1)在基础状态及胰岛素刺激下,3T3-L1脂肪细胞葡萄糖摄取随Retn基因表达的升高而降低。(2)PI-3K和AKT-2两个信号蛋白mRNA的表达随着细胞内Retn基因表达水平的升高而降低;GSK-3β和p38MAPK两个信号蛋白mRNA的表达随着细胞内Retn基因表达水平的升高而升高。结论:(1)Resistin蛋白可以导致脂肪细胞产生胰岛素抗性,其机制可能与胰岛素信号通路中的PI-3K和Ras通路中一些信号蛋白表达的变化有关。Objective:To investigate the influence of high expression of Retn gene on glucose uptake by 3T3-L1 cells and to study its mechanism in inducing insulin resistance. Methods: (1)Radioimmunoassay was used to determine the glucose uptake hy 3T3-L1 cells with low-, normal- and high-level Retn expression under basal and insulin-stimulated states. (2)RT PCR and real-time RT-PCR were used to determine the mRNA levels of several glucose transport proteins in 3T3-L1 cells with different expression of Retn, including insulin receptor suhstrate-1 (IRS-1), phosphatidylinositol 3-kinase (PI-3K), AKT-2, glucose transporter-4 (GLUT-4), p38 mitogen-activated protein kinase (p38MAPK), and glycogen synthase kinase-31?(GSK-31?). Results: The uptake of glucose decreased with the increase of Retn expression under basal and insulin-stimulated conditions. The mRNA expression of 2 signal protein PI-3K and AKT-2 decreased with the increase of Retn expression; and the expression of GSK-31β and p38MAPK increased with the increase of Retn expression. Conclusion: Resistin protein can induce insulin resistance in adipocytes, which might he related to the expression changes of some proteins in PI-3K and Ras pathways.
关 键 词:resistin蛋白 Retn基因 胰岛素 葡萄糖摄取 3T3-L1细胞
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